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Keywords:

  • Alzheimer's disease;
  • apoptosis;
  • incretins;
  • insulin;
  • neurodegeneration;
  • neuroprotection

Abstract

Thumbnail image of graphical abstract

Glucagon-like peptide 1 (GLP-1) is a growth factor that has demonstrated neuroprotective properties in a range of studies. In an APPswe/PS1ΔE9 mouse model of Alzheimer's disease (AD), we previously found protective effects on memory formation, synaptic plasticity, synapse survival and a reduction of amyloid synthesis and plaque load in the brain. Here, we analyse the neuroprotective properties of the GLP-1 analogue liraglutide in human neuroblastoma cell line SH-SY5Y during methyl glyoxal stress. We show for the first time that cell viability was enhanced by liraglutide (XTT assay) in a dose-dependent way, while cytotoxicity (LDH assay) and apoptosis were reduced. Expression of the pro-survival Mcl1 signaling protein was increased, as was activation of cell survival kinases Akt, MEK1/2 and the transcription factor p90RSK. Liraglutide also decreased pro-apoptotic Bax and Bik expression. In addition, the membrane potential and the influx of calcium into the cell were enhanced by liraglutide. GLP-1 receptor expression was also increased by the drug. The results demonstrate a range of growth factor-related cytoprotective processes induced by liraglutide, which is currently on the market as a treatment for type 2 diabetes (Victoza®). It is also tested in clinical trials in patients with Alzheimer disease.

We investigated the neuroprotective properties of the GLP-1 analogue liraglutide in SH-SY5Y cells during methyl glyoxal stress. Cell survival was enhanced, while cytotoxicity and apoptosis was reduced. Expression of the pro-survival Mcl1 signaling protein, activation of Akt, MEK1/2 and the transcription factor p90RSK was increased. Pro-apoptotic Bax and Bik expression was reduced, and the influx of calcium into the cell was normalised. The results demonstrate a range of growth factor related cytoprotective processes induced by the drug liraglutide.